FYN

PRESS RELEASE AB SCIENCE RECEIVES NOTICE OF ALLOWANCE FOR EUROPEAN PATENT COVERING MASITINIB UNTIL 2040 IN THE TREATMENT OF SICKLE CELL DISEASE THIS DECISION FURTHER STRENGTHENS MASITINIB’S INTELLECTUAL PROPERTY ADDING ONE MORE INDICATION WITH LONG TERM PROTECTION MASITINIB IS IN PHASE 2 IN SICKLE CELL DISEASE Paris, October 28, 2024, 5.45pm CET AB Science SA (Euronext - FR0010557264 - AB) today announced that the European Patent Office has issued a Notice of Allowance for a patent relating to methods of treating sickle cell disease (i.e. a medical use patent) with its lead compound masitinib, based on preclinical data. This new European patent provides intellectual property protection for masitinib in this indication until November 2040. Professor Olivier Hermine, President of the AB Science Scientific Committee and member of the French Academy of Sciences and Head of Hematology Department at Necker Hospital commented: “Masitinib represents a promising novel strategy for treating sickle cell disease and its serious complication of acute chest syndrome, which can lead to the development of chronic lung disease and is a common cause of hospitalization or even death. There is an increasing need in sickle cell disease with several new drugs being retrieved from market for lack of efficacy or toxicity; however, unlike masitinib, none of these drugs target mast cells”. Sickle cell disease (SCD) is a group of inherited red blood cell disorders, with masitinib being developed to treat the severest forms of the disease, accounting for about 65% of SCD. Severe SCD represents a major public health challenge and leads to early death. Treatment for SCD can be curative based on gene therapy (targets the HbS mutation), however, such an option remains extremely limited due to scarcity of donors, unresolved safety challenges, and very high costs. Standard treatment for SCD includes ​​red blood cell transfusions and treatment with hydroxyurea to manage complications, but significant unmet need remains. Mast cells, a major target for masitinib, appear to play a critical role for the severe forms of SCD and its complications, such as vaso-occlusive crises (VOC), acute chest syndrome (ACS), and pain [1-2]. Masitinib has demonstrated survival benefit in an SCD mouse model: all control SCD mice experienced VOC and 83% died in the first 3 hours, whereas SCD mice pretreated with masitinib for 4 days, experienced no VOCs and no death. Furthermore, lung histology and immune immunohistochemistry showed that masitinib protects from acute lung injuries and mast cell infiltration in an SCD mouse model. Masitinib clinical development in SCD is being conducted as part of the SICKMAST collaborative program, funded with 9.2 million euros [3], which aims to demonstrate in a phase 2 clinical trial the efficacy of masitinib in the treatment of acute and chronic complications of SCD in patients identified based on biomarkers. The Assistance Publique-Hôpitaux de Paris (AP-HP) will be the promoter of these phase 2 studies. AB Science will mainly be involved in supplying masitinib and monitoring masitinib pharmacovigilance data. AB Science remains free to carry out, as it sees fit, any potential phase 3 development following the success of phase 2. Sickle cell disease Sickle cell disease (SCD) is an autosomal recessive disorder affecting millions of people worldwide. Although life expectancy has increased over the last 20 years, acute and chronic complications still result in comorbidities, high social burden and premature death at around 40 years. Approximately 1.1% of couples worldwide are at risk of having a child with a hemoglobin disorder (sickle cell disease or thalassemia), and 2.3 conceptions per 1,000 are affected by sickle cell disease. Estimates suggest that each year, around 300,000 children are born with sickle cell disease, and this number could reach 400,000 by 2050 [4]. Sickle cell disease affects over 100,000 children and adults in the United States. In France, approximately 26,000 patients are affected (50% children, 50% adults). Rationale for the use of masitinib in this indication Inflammation mediated by innate immune cells and promoting vaso-occlusion has recently been shown to play a major role in sickle cell disease. In particular, our clinical observations and experimental work in mice, have revealed the involvement of mast cells and basophils in complications associated with sickle cell disease: The degree of mast cell activation in patients with sickle cell disease may contribute to the heterogeneity of inflammation and chronic and acute complications.The potential role of basophils in sickle cell disease has not been studied, however, given their role in various diseases and their ability to release substance P and histamine, they could also play important roles in the pathophysiology of sickle cell disease. Masitinib is an inhibitor of KIT, LYN, and FYN, three major kinases involved in the activation of mast cells and basophils. Medical need The classic view of sickle cell disease pathophysiology involves polymerization of mutated hemoglobin (HbS) leading to red blood cell (RBC) sickling with subsequent hemolytic anemia, painful vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). Current treatment options such as hydroxycarbamide, chronic transfusion or anti-P-selectin antibodies, do not fully prevent life-threatening acute and chronic complications of sickle cell disease. Allogeneic stem cell transplantation and gene therapy are available only for a minority of patients, are associated with toxicity and are very expensive, which limits their use. There is a significant medical need to prevent the acute and chronic complications of sickle cell disease. References [1] Allali S, Lionnet F, Mattioni S, et al. Br J Haematol. 2019;186(1):125-129. [2] Allali S, Maciel TT, Hermine O, de Montalembert M. Haematologica. 2020;105(2):273-283. [3] AB Science Press Release, 27th November 2023. https://www.ab-science.com/the-clinical-development-of-masitinib-in-sickle-cell-disease-is-among-the-19-winning-projects-under-the-sixth-call-for-hospital-inuversity-research-in-health-rhu/ [4] Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med. 2017;376(16):1561-1573. About AB Science Founded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB Science This press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB Science Financial Communication & Media Relations investors@ab-science.com Attachment Sickle Cell Patent EPO vENG VF

On July 29, Boehringer Ingelheim announced a major acquisition, with plans to buy Nerio Therapeutics for $1.3 billion. Nerio Therapeutics, a pharmaceutical company focused on phosphatase research, has successfully developed highly selective phosphatase PTPN2/N1 inhibitors for an innovative regimen of tumor immunotherapy. With a leading position in the global oncology market, Boehringer Ingelheim has continuously strengthened its strategic presence in oncology in recent years. According to preliminary statistics, the company has established cooperative relationships with a number of well-known pharmaceutical companies in recent years to accelerate the construction of tumor research and development pipelines: In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to acquire novel antibody-coupled drugs to address the challenge of refractory solid tumors. In the same month, Boehringer Ingelheim acquired Labor Dr. Merk & Kollegen to increase its research and development and clinical manufacturing capabilities to support its next generation cancer immune drug development program. In January 2021, the company entered into a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using its Dark Antigen™ platform. In September 2021, Boehringer Ingelheim acquired Abexxa Biologics to gain expertise in targeting cancer-specific proteins within cells, expanding the range of potential cancer antigen targets. In June 2022, the company entered into A global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to acquire the development and commercialization rights for A*STAR's series of innovative tumor-specific antibodies. In January 2023, Boehringer Ingelheim and 3T Biosciences entered into a strategic collaboration and licensing agreement to jointly explore and develop the next generation of cancer therapies. In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate for the ADAR1 cancer target. In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), which specializes in innovative therapeutic platforms that enhance immunotherapy with live bacteria. In the same month, Boehringer Ingelheim established a strategic collaboration and licensing agreement with Phenomic AI to jointly discover key targets in rich stromal cancers. In February 2024, Boehringer Ingelheim and CBmed entered into a long-term strategic partnership to accelerate the development of first-of-its-kind oncology drugs using translational medicine to improve the lives of patients. In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to jointly develop first-of-its-kind therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor Immunity program and the cis targeted anti-PD1 / cytokine platform. While Boehringer Ingelheim does not yet have a significant oncology product in the market, its oncology pipeline includes several promising candidates, such as Zongertinib(Phase 1), Brigimadlin (Phase two-thirds) and BI-764532 (Phase 2). Zongertinib is an innovative covalently bound, orally effective and selective HER2 small molecule inhibitor. It covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including exon 20 mutations, while preserving the wild-type signal of EGFR, thereby demonstrating good tolerability and safety while ensuring efficacy. Data from the Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors (NCT04886804), presented at the ASCO meeting in 2024, showed that Zongertinib demonstrated superior efficacy and was well tolerated in patients with HER2-mutation-positive advanced NSCLC. Brigimadlin is a mouse dual microhomologous gene 2 (MDM2) -p53 antagonist targeting MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. Currently, Brigimadlin's first-line treatment of dedifferentiated liposarcoma (DDLPS) has entered phase 2/3 of clinical trials. New results from the Phase 1a/1b study (NCT03449381) presented at the ASCO Meeting in 2024 show that Brigimadlin induces proteomic changes in DDLPS that may serve as potential biomarkers for predicting treatment response and adverse events. BI 764532 is a first-in-class T cell-mediated bisspecific antibody developed at Boehringer Ingelheim that induces a patient's own T cells to attack cancer cells expressing DLL3. BI 764532 has received fast track approval from the FDA for the treatment of advanced SCLC and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 showed potential preclinical antitumor activity. PTPN2 and PTPN1 (also known as PTP-1B) are phosphatases that negatively regulate multiple cytokine signaling pathways and T cell receptor (TCR) signaling pathways. They inhibit inflammation by dephosphorylation of JAK and STAT family members, and reduce T-cell sensitivity to antigens by phosphorylation of LCK and FYN. PTPN2 deletion was found to increase the number of activated cytotoxic CD8+T cells in the tumor, improve antigen presentation and sensitivity to IFNγ, and thus enhance tumor sensitivity to CD8+T cells. Given the critical role of PTPN2/N1 in tumor and immune cells and its highly conserved active sites, researchers are developing PTPN2/N1 inhibitors. Currently, there are several PTPN2/N1 inhibitors, such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484 is an oral PTPN2/N1 active site inhibitor that enhances the response to interferon and promotes the activation and function of immune cell subsets. In a PD-1-resistant mouse model, AC484 monotherapy showed significant antitumor effects. Currently, a Phase 1 clinical trial of AC484 is underway to evaluate its efficacy alone or in combination with PD-1 inhibitors or VEGFR tyrosine kinase inhibitors (TKI) in the treatment of advanced or metastatic solid tumors. In addition, using Chemistry42, its generating-AI platform, Insili has also developed a novel PTPN2/N1 inhibitor that has drug-like properties, good oral bioavailability in vivo, and strong in vivo anti-tumor activity, demonstrating nanoscale inhibitory efficacy.

KeifeRx is currently advancing programs investigating KFRX03, KFRX04, KFXR05 and KFX06 in neurodegenerative, neuroinflammatory, and mast cell-associated diseases WASHINGTON, Jan. 8, 2024 /PRNewswire/ -- KeifeRx, an emerging clinical-stage biopharmaceutical company specializing in the discovery and development of new treatment options for neurodegenerative and immune diseases, announced today entry into an amended exclusive licensing agreement with Georgetown University to advance the development of novel tyrosine kinase inhibitor (TKI) chemical entities (NCE) for the treatment of multiple disease indications. The amendment provides an extension of the exclusively licensed rights to these four novel chemical entities for the treatment of new disease conditions including inflammatory, mast-cell associated diseases, and oncology, in addition to existing rights in neurodegenerative diseases. KeifeRx is currently conducting optimizing and IND-enabling studies involving four separate formulations of the TKI (renamed KFRX03, KFRX04, KFRX05, and KFRX06) with patent life through 2037. Early-stage clinical trials conducted at Georgetown University, along with compelling preclinical research conducted at the university led by KeifeRx's co-founder, Charbel Moussa, MBBS, Ph.D., and colleagues, demonstrated the ability of TKIs to penetrate the brain, induce autophagy, and enable the bulk disposal of disease-causing toxic proteins to treat neurodegenerative diseases, as well as the ability to target mast cells and simultaneously modulate peripheral and central immunity, providing therapeutic potential for an array of immune diseases. These properties offer the potential to significantly improve upon current neurodegenerative and immune disease treatments, which are primarily palliative and offer minimal and temporary benefits due to their inability to adequately eliminate toxic proteins and mitigate inflammation. "Entry into this expanded exclusive licensing agreement with Georgetown is a pivotal milestone for the growth of KeifeRx as we have significantly increased the range of indications we can pursue with our portfolio of new chemical entity TKIs, including the treatment of neurodegenerative, neuroinflammatory, and mast cell-related diseases," said Chris Hoyt, Chief Executive Officer of KeifeRx. "We look forward to working with the research team at Georgetown University to spearhead the development of KFRX03, KFRX04, KFRX05, and KFRX06 for the treatment of multiple, underserved disease indications. The IP covering these assets extends through 2037, making the portfolio a high-value drug opportunity given its numerous potential disease indications, including Alzheimer's disease, ALS, mast cell activation syndrome (MCAS), and urticaria." About KeifeRx KeifeRx is an emerging clinical-stage biopharmaceutical company developing a portfolio of novel and optimized, low-dose, orally-delivered tyrosine kinase inhibitors (TKIs) for the treatment of multiple, high-need neurodegenerative and immune diseases, including Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Lewy Body Dementia. KeifeRx's diverse pipeline of early- and late-stage products leverages mechanisms of action inherent to TKIs which thus far have been underexplored. This includes the ability to penetrate the brain, induce autophagy, and enable the bulk disposal of disease-causing toxic proteins to treat neurodegenerative diseases. Georgetown University owns several issued patents and pending patent applications on the underlying technology related to the use of TKIs for the treatment of neurodegenerative diseases with KeifeRx co-founder Charbel Moussa, MBBS, Ph.D., named as one of three inventors. KeifeRx has an exclusive license to the intellectual property from Georgetown University. For more information on KeifeRx, please visit . For more information, please contact: Tiberend Strategic Advisors, Inc. Daniel Kontoh-Boateng (Investors) dboateng@tiberend.com David Irish (Investors) dirish@tiberend.com Jason Rando (Media) jrando@tiberend.com View original content to download multimedia: SOURCE KeifeRx, LLC